Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

The pathogenicity and immune effects of different generations of Mycoplasma synoviae on chicken embryos.

1. Mycoplasma synoviae (MS) is the primary causative agent of synovitis in avian species. In order to investigate the pathogenicity and immunological responses associated with MS in specific pathogen-free chicken embryos, a series of generations (F1, F95, F120, F160 and F200) of MS were introduced into 7-day-old SPF chicken embryos and subsequent mortality rates were recorded and analysed2. Reverse transcription-quantitative polymerase chain reaction was performed to detect expression of heat shock proteins HSP27, HSP40, HSP60, HSP70 and HSP90 and inflammatory factors interleukin (IL)-1ß, caspase-1 and IL-18 in the tracheal tissue.3. The results showed that the mortality rate of SPF chicken embryos decreased with an increase in the number of passages, with the highest being 80% (8/10) for F1 generation and the lowest being 10% (1/10) for F200. The expression of HSP27, IL-1ß, HSP40, caspase-1, HSP70 and HSP90 showed a significant downregulation trend with an increase in the generation (except IL-18; P < 0.05). The HSP60 expression was significantly upregulated with increasing generations (P < 0.05).4. A relationship between pathogenicity and the number of passages was observed and the decrease in pathogenicity appeared to be associated with HSP and genes related to inflammatory factors. The present work offers a scientific foundation for screening potential MS strains that might be employed to develop attenuated vaccines.

[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

[Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms].

Objective: To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Methods: This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment. Results: Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions: The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

[Comparison of robotic-assisted single-incision-plus-one-port laparoscopic pyeloplasty and single-incision laparoscopic pyeloplasty in the treatment of pediatric ureteropelvic junction obstruction].

Objective: To compare the efficacy of robotic-assisted single-incision-plus- one-port laparoscopic pyeloplasty (R-SILP+1) with single-incision laparoscopic pyeloplasty (SILP) in pediatric ureteropelvic junction obstruction (UPJO). Methods: The clinical data of 47 children with UPJO who underwent surgery from October 2020 to September 2022 in the Department of Pediatric Surgery of Fujian Provincial Hospital were retrospectively analyzed. According to the surgical method chosen by parents, the children were divided into R-SILP+1 group and SILP group. Baseline data, operative time, intraoperative anastomosis time, volume of blood loss, postoperative hospitalization time, complications, total costs, preoperative and postoperative renal parenchymal thickness (PT), anterior posterior diameter of renal pelvis (APD), and differential renal function (DRF) before and after operation were compared between the two groups, and the clinical efficacy of the two kinds of operation was evaluated. Results: Among the 47 children, 27 were in R-SILP+1 group, including 16 males and 11 females, aged (6.6±3.5) years; 20 were in SILP group, including 12 males and 8 females, aged (6.5±3.5) years. The operations were successful in both groups without conversion to open operation. There were no significant differences between the two groups in baseline data, volume of blood loss, complications, APD and PT at postoperative 6 months, APD, PT and DRF at postoperative 12 months (all P>0.05). Compared with the SILP group, the operative time [(153.0±14.4) vs (189.9±32.6) minutes, P<0.001], intraoperative anastomosis time [(68.8±16.8) vs (97.5±12.0) minutes, P<0.001], postoperative hospitalization time [(6.0±1.3) vs (9.0±1.3) d, P<0.001] were shorter, but the total cost was higher[(57 390±7 664) vs (30 183±4 219) yuan RMB, P<0.001]. Conclusions: Compared with the SILP group, R-SILP+1 can achieve considerable efficacy in treating pediatric UPJO, and has certain advantages in shortening operative time, intraoperative anastomosis time, and postoperative hospitalization time. However, the cost is high.

[The mechanism of NRF2 inhibiting ROS induced autophagy to reduce ovarian granulosa cells damage].

This study explores the effects and possible mechanisms of nuclear factor E2 related factor 2 (NRF2) on ovarian granulosa cells, providing a scientific basis to prevent premature ovarian failure. An ovarian cell injury model was constructed by treating human ovarian granulosa cell (KGN cell) with 4-Vinylcyclohexene dioxide (VCD). Firstly, KGN cells were treated with different concentrations of VCD, and cell counting kit 8 (CCK-8) was used to detect ovarian cell proliferation. After determining IC50 by CCK8, the levels of estradiol and progesterone in the cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) assay kit was used to detect the content of ROS in ovarian cells, real-time fluorescence quantitative polymerase chain reaction (qRT PCR) was used to detect the mRNA expression level of NRF2, and Western blot was used to detect the protein expression level of NRF2. Further, NRF2 silence (siNRF2) and overexpression (NRF2-OE) cell models were constructed through lentivirus transfection, and the effects of regulating NRF2 on VCD treated cell models were investigated by detecting hormone levels, oxidative stress indicators (ROS, SOD, GSH-Px), and autophagy (LC3B level). The results showed that VCD intervention inhibited the proliferation of ovarian granulosa cells in a time-dependent and dose-dependent manner (F>100, P<0.05), with an IC50 of 1.2 mmol/L at 24 hours. After VCD treatment, the level of estradiol in the cell supernatant decreased from (56.32±10.18) ng/ml to (24.59±8.75) ng/ml (t=5.78, P<0.05). Progesterone decreased from (50.25±7.03) ng/ml to (25.13±6.67) ng/ml (t=6.54, P<0.05). After VCD treatment, the SOD of cells decreased from (44.47±7.71) ng/ml to (30.92±4.97) ng/ml (t=3.61, P<0.05). GSH-Px decreased from (68.51±10.17) ng/ml to (35.19±6.59) ng/ml (t=5.73, P<0.05). Simultaneously accompanied by an increase in autophagy and a decrease in NRF2. This study successfully constructed KGN cell models that silenced NRF2 and overexpressed NRF2. Subsequently, this study treated each group of cells with VCD and found that the cell proliferation activity of the siNRF2 group was significantly reduced (t=8.37, P<0.05), while NRF2-OE could reverse the cell activity damage caused by VCD (t=3.37, P<0.05). The siNRF2 group had the lowest level of estradiol (t=5.78, P<0.05), while NRF2-OE could reverse the decrease in cellular estradiol levels caused by VCD (t=5.58, P<0.05). The siNRF2 group had the lowest progesterone levels (t=3.02, P<0.05), while NRF2-OE could reverse the decrease in cellular progesterone levels caused by VCD (t=2.41, P<0.05). The ROS level in the siNRF2 group was the highest (t=2.86, P<0.05), NRF2-OE could reverse the increase in ROS caused by VCD (t=3.14, P<0.05), the SOD enzyme content in the siNRF2 group was the lowest (t=2.98, P<0.05), and NRF2-OE could reverse the decrease in SOD enzyme content caused by VCD (t=4.72, P<0.05). The GSH-Px enzyme content in the siNRF2 group was the lowest (t=3.67, P<0.05), and NRF2-OE could reverse the decrease in antioxidant enzyme content caused by VCD (t=2.71, P<0.05). The LC3B level was highest in the siNRF2 group (t=2.45, P<0.05), and NRF2-OE was able to reverse the LC3B elevation caused by VCD (t=9.64, P<0.05). In conclusion, NRF2 inhibits ROS induced autophagy, thereby playing a role in reducing ovarian granulosa cell damage, which may be a potential target for premature ovarian failure.

[Practical application of the Paris system for reporting urinary cytology].

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

AI Chatbots in Clinical Laboratory Medicine: Foundations and Trends.

BACKGROUND: Artificial intelligence (AI) conversational agents, or chatbots, are computer programs designed to simulate human conversations using natural language processing. They offer diverse functions and applications across an expanding range of healthcare domains. However, their roles in laboratory medicine remain unclear, as their accuracy, repeatability, and ability to interpret complex laboratory data have yet to be rigorously evaluated. CONTENT: This review provides an overview of the history of chatbots, two major chatbot development approaches, and their respective advantages and limitations. We discuss the capabilities and potential applications of chatbots in healthcare, focusing on the laboratory medicine field. Recent evaluations of chatbot performance are presented, with a special emphasis on large language models such as the Chat Generative Pre-trained Transformer in response to laboratory medicine questions across different categories, such as medical knowledge, laboratory operations, regulations, and interpretation of laboratory results as related to clinical context. We analyze the causes of chatbots' limitations and suggest research directions for developing more accurate, reliable, and manageable chatbots for applications in laboratory medicine. SUMMARY: Chatbots, which are rapidly evolving AI applications, hold tremendous potential to improve medical education, provide timely responses to clinical inquiries concerning laboratory tests, assist in interpreting laboratory results, and facilitate communication among patients, physicians, and laboratorians. Nevertheless, users should be vigilant of existing chatbots' limitations, such as misinformation, inconsistencies, and lack of human-like reasoning abilities. To be effectively used in laboratory medicine, chatbots must undergo extensive training on rigorously validated medical knowledge and be thoroughly evaluated against standard clinical practice.

Generalizability of a Machine Learning Model for Improving Utilization of Parathyroid Hormone-Related Peptide Testing across Multiple Clinical Centers.

BACKGROUND: Measuring parathyroid hormone-related peptide (PTHrP) helps diagnose the humoral hypercalcemia of malignancy, but is often ordered for patients with low pretest probability, resulting in poor test utilization. Manual review of results to identify inappropriate PTHrP orders is a cumbersome process. METHODS: Using a dataset of 1330 patients from a single institute, we developed a machine learning (ML) model to predict abnormal PTHrP results. We then evaluated the performance of the model on two external datasets. Different strategies (model transporting, retraining, rebuilding, and fine-tuning) were investigated to improve model generalizability. Maximum mean discrepancy (MMD) was adopted to quantify the shift of data distributions across different datasets. RESULTS: The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.936, and a specificity of 0.842 at 0.900 sensitivity in the development cohort. Directly transporting this model to two external datasets resulted in a deterioration of AUROC to 0.838 and 0.737, with the latter having a larger MMD corresponding to a greater data shift compared to the original dataset. Model rebuilding using site-specific data improved AUROC to 0.891 and 0.837 on the two sites, respectively. When external data is insufficient for retraining, a fine-tuning strategy also improved model utility. CONCLUSIONS: ML offers promise to improve PTHrP test utilization while relieving the burden of manual review. Transporting a ready-made model to external datasets may lead to performance deterioration due to data distribution shift. Model retraining or rebuilding could improve generalizability when there are enough data, and model fine-tuning may be favorable when site-specific data is limited.

High-Flux Neutron Generator Based on Laser-Driven Collisionless Shock Acceleration.

A novel compact high-flux neutron generator with a pitcher-catcher configuration based on laser-driven collisionless shock acceleration (CSA) is proposed and experimentally verified. Different from those that previously relied on target normal sheath acceleration (TNSA), CSA in nature favors not only acceleration of deuterons (instead of hydrogen contaminants) but also increasing of the number of deuterons in the high-energy range, therefore having great advantages for production of high-flux neutron source. The proof-of-principle experiment has observed a typical CSA plateau feature from 2 to 6 MeV in deuteron energy spectrum and measured a forward neutron flux with yield 6.6×10^{7} n/sr from the LiF catcher target, an order of magnitude higher than the compared TNSA case, where the laser intensity is 10^{19} W/cm^{2}. Self-consistent simulations have reproduced the experimental results and predicted that a high-flux forward neutron source with yield up to 5×10^{10} n/sr can be obtained when laser intensity increases to 10^{21} W/cm^{2} under the same laser energy.

Evidence for Band Renormalizations in Strong-Coupling Superconducting Alkali-Fulleride Films.

There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of superconducting K_{3}C_{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k_{B}T_{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K_{3}C_{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.

Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study.

BACKGROUND: Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results. OBJECTIVE: To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety. DESIGN: Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control. PARTICIPANTS: Consecutive emergency department (ED) patients with at least one cTn test resulted. INTERVENTION: Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection. MAIN MEASURES: Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences. KEY RESULTS: The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81). CONCLUSIONS: Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.

Spin-dependent thermoelectric transport properties of Cr-doped blue phosphorene.

We systematically investigate the thermoelectric (TE) properties of the Cr-doped blue phosphorene (blue-P) along the armchair and zigzag directions. First, we find the semiconducting band structure of the blue-P will become spin-polarized due to the Cr-doping, and can be seriously changed by the doping concentration. Then we show the Seebeck coefficient, the electronic conductance, the thermal conductance, and the figures of meritZTs are all dependent on the transport directions and doping concentration. However, two pairs of the peaks of the charge and spinZTs can be always observed with the low-height (high-height) pair on the side of the negative (positive) Fermi energy. In addition, at temperature 300 K the extrema of the charge (spin)ZTs of the blue-P along the two directions are kept to be larger than 22 (90) for the different doping concentrations and will be further enhanced at lower temperature. Therefore, we believe the Cr-doped blue-P should be a versatile high-performance TE material which may be used in the fields of the thermorelectrics and spin caloritronics.

Elevated levels of renal function tests conferred increased risks of developing various pregnancy complications and adverse perinatal outcomes: insights from a population-based cohort study.

OBJECTIVES: Physiological changes during pregnancy can affect the results of renal function tests (RFTs). In this population-based cohort study, we aimed to establish trimester-specific reference intervals (RIs) of RFTs in singleton and twin pregnancies and systematically investigate the relationship between RFTs and adverse pregnancy outcomes. METHODS: The laboratory results of the first- and third-trimester RFTs, including blood urea nitrogen (BUN), serum uric acid (UA), creatinine (Crea) and cystatin C (Cys C), and the relevant medical records, were retrieved from 29,328 singleton and 840 twin pregnant women who underwent antenatal examinations from November 20, 2017 to January 31, 2021. The trimester-specific RIs of RFTs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between RTFs and pregnancy complications as well as perinatal outcomes were assessed by logistic regression analysis. RESULTS: Maternal RFTs showed no significant difference between the direct RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. In addition, elevated levels of RFTs were associated with increased risks of developing various pregnancy complications and adverse perinatal outcomes. Notably, elevated third-trimester RFTs posed strong risks of preterm birth (PTB) and fetal growth restriction (FGR). CONCLUSIONS: We established the trimester-specific RIs of RFTs in both singleton and twin pregnancies. Our risk analysis findings underscored the importance of RFTs in identifying women at high risks of developing adverse complications or outcomes during pregnancy.

Electronic structures, transport properties, and optical absorption of bilayer blue phosphorene nanoribbons.

Based on first-principles density functional theory and nonequilibrium Green's function, we study the electronic band structures, the electronic transport properties, and the optical absorption of bilayer blue phosphorene nanoribbons (BPNRs). Both bilayer armchair BPNRs (a-BPNRs) and zigzag BPNRs (z-BPNRs) behave as semiconductors in the narrow nanoribbon case and metals in the wide nanoribbon case, sharply different from their monolayer counterparts where the monolayer a-BPNRs (z-BPNRs) are always semiconducting (metallic). This indicates that interlayer couplings or the increasing layer number may induce the switching of the conductivity of the monolayer BPNRs, which is absent in graphene and phosphorene nanoribbons. Furthermore, we explore the edge states of the energy bands near Fermi energy, and find that there are almost no pure edge-state band branches in the bilayer BPNRs, which can be attributed to the interlayer couplings between the edge-states in one layer and the bulk-states in the other. Consequently, the resulting complex band structures cannot be directly analyzed any more in the framework of the two-body coupling picture just according to the simple band structures of the monolayer BPNRs. Finally, we present the current-voltage characteristics and the optical absorption of the bilayer a-BPNRs and z-BPNRs. The influences of the nanoribbon width and the interlayer couplings on the current and the anisotropic optical absorption can be understood based on the complex energy band structures. This research should be an important reference of extending the field of BPNRs from the monolayer to the bilayer case, and deepen the understanding of the difference between the monolayer and bilayer nanoribbons in different materials.

Multidetector CT-derived tricuspid annulus measurements predict tricuspid regurgitation reduction after transcatheter aortic valve replacement.

AIM: To use multidetector row computed tomography (MDCT)-derived tricuspid annulus (TA) measurements to identify predictors for tricuspid regurgitation (TR) reduction after transcatheter aortic valve replacement (TAVR), and to investigate the impact of TR change on prognosis. MATERIALS AND METHODS: A retrospective, single-centre study was conducted on consecutive patients who underwent TAVR with concomitant baseline mild or more severe TR from April 2012 to April 2022. TA parameters were measured using MDCT. RESULTS: The study comprised 266 patients (mean age 74.2 ± 7.6 years, 147 men) and 45.1% had more than one grade of TR reduction at follow-up. Independent predictors of TR reduction at follow-up were distance between TA centroid and antero-septal commissure (odd ratio [OR] 0.776; 95% confidence interval [CI]: 0.672-0.896, p=0.001), baseline TR of moderate or worse (OR 4.599; 95% CI: 2.193-9.648, p<0.001), systolic pulmonary artery pressure (OR 1.018; 95% CI: 1.002-1.035, p=0.027), age (OR 0.955; 95% CI: 0.920-0.993, p=0.019), and pre-existing atrial fibrillation (OR 0.209; 95% CI: 0.101-0.433, p<0.001). Patients without TR reduction had higher rates of rehospitalisation (hazard ratio [HR] 0.642; 95% CI: 0.413-0.998, p=0.049). CONCLUSIONS: The MDCT-derived TA parameter was predictive of TR reduction after TAVR. Persistent TR after TAVR was associated with higher rates of rehospitalisation.

Modifiable predictors of type 2 diabetes mellitus and roles of insulin resistance and ß-cell function over a 6-year study and 30-year follow-up.

PURPOSE: This study aimed to examine the modifiable predictors of T2DM and the roles of insulin resistance (IR) and ß-cell function over a 6-year study and 30-year follow-up. METHODS: A total of 462 non-diabetic participants, 282 with impaired glucose tolerance (IGT), and 180 with normal glucose tolerance (NGT) were enrolled in this analysis. The Matsuda IR index and area under the curve of insulin-to-glucose ratio (AUCI/G-R) were used as IR and ß-cell function indices in the analysis. RESULTS: In all participants, multivariable analysis showed that BMI, glucose status, Matsuda IR index and systolic blood pressure (SBP) at baseline were independently associated with an increased risk of T2DM over 30 years, whereas lifestyle intervention and AUCI/G-R were inversely associated with this risk. The predictive effect of the Matsuda IR index and AUCI/G-R in participants with IGT was consistent with the results of all participants, whereas in those with NGT, only the Matsuda IR index, not the AUCI/G-R, predicted the development of T2DM (HR = 1.42, 95% CI 1.07-1.89 vs HR = 1.09, 95% CI 0.76-1.56). The predictive effect of the Matsuda IR index on T2DM existed even in participants with BMI < 25 (p = 0.049). CONCLUSION: The modifiable predictors of T2DM in Chinese adults were high BMI, hypertension, mild hyperglycaemia, IR, and ß-cell dysfunction. Both IR and ß-cell function contributed to the development of T2DM in the long term; however, IR remains the initial and long-standing key risk factor for T2DM.

[Endoscopic hand-suturing combined with titanium clips for rectal defects closure after endoscopic submucosal dissection: a pilot study].

Objective: To explore the feasibility of endoscopic hand-suturing (EHS) for rectal defects closure after endoscopic submucosal dissection (ESD), and the clinical practicability of EHS combined with titanium clips. Methods: This is a prospective study performed by two experienced endoscopists from the Cancer Hospital, Chinese Academy of Medical Sciences who had received EHS training in sixporcine gastric ESD defects in vivo before the study. From December 2022 to February 2022, 20 patients with rectal mucosal lesions or submucosal diseases underwent ESD. Then EHS combined with titanium clips was adopted to close the rectal ESD defects. Specifically, we first sutured the defects as much as possible through EHS, then use titanium clips to fix the tail of the suture, and finally use additional titanium clips to close the residual parts of the defects that cannot be sutured. The main observational indicators were complete closure of the wound and delayed bleeding within one month after surgery. Results: In the 20 rectal cases, the size of defects ranged from 2.2 to 3.6 cm, with a median of 2.7 cm. All cases achieved complete closure without delayed bleeding, of which 12 (60.0%) were completely sutured with EHS and 8 (40.0%) required additional titanium clips to achieve complete closure after suturing. Conclusion: EHS technique is feasible and safe for rectum. EHS combined with titanium clips can also effectively close the rectal ESD defects, prevent postoperative delayed bleeding, and may be easier to be implemented in clinical practice.

[Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion].

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.